1. Field of the Invention
This invention relates to 1-oxygenated-1,2,3,4,5,6-hexahydro-6-alkyl-11-(hydrogen or alkyl)-2,6-methano-3-benzazocines and intermediates and processes therefor.
2. Prior Art Statement
The only 1-oxygenated-1,2,3,4,5,6-hexahydro-6-alkyl-11-(hydrogen or alkyl)-2,6-methano-3-benzazocines of the prior art known to me are three compounds described by Ziering (et al., J. Med. Chem. vol. 13, pp. 9-13, 1970) as having in the free base form the structural formulas
______________________________________ ##STR1## Compound X.sup.2 X.sup.1 ______________________________________ 12 -- O 13 OH C.sub.6 H.sub.5 14 OH CH.sub.3 ______________________________________
The three compounds were prepared primarily as intermediates from which the 1-oxygen functions were removed to provide 1-(phenyl or methyl)-1,2,3,4,5,6-hexahydro-6,11-dimethyl-2,6-methano-3-benzazocines, but were incidentally tested for analgesic, anti-inflammatory and antiedema, and morphine antagonist activity. Compound 12 (as the hydrochloride salt) was inactive in all tests except the morphine antagonist test in the mouse. Before the publication of the Ziering reference, compound 12 (as the free base) was prepared under my direction in my laboratory and was tested for morphine antagonist and meperidine antagonist activity in the rat. The compound was inactive against morphine and weakly active against meperidine and is therefore not a true antagonist. Compounds 13 and 14 are reported by the Ziering reference to be weakly active in the writhing test for analgesia in the mouse, and inactive in all other tests. The Ziering reference states in summary that compounds 12-14 would be of no further interest as analgesics, anti-inflammatories or morphine antagonists. In spite of the conclusion of the Ziering reference and the implication thereof that 1-oxygenation does not produce valuable biological properties in 1,2,3,4,5,6-hexahydro-6-alkyl-11-(hydrogen or alkyl)-2,6-methano-3-benzazocines, I have prepared, or have had others prepare certain new 1-oxygenated 1,2,3,4,5,6-hexahydro-6-alkyl-11-(hydrogen or alkyl)-2,6-methano-3-benzazocines which in fact do have valuable biological properties and which I now describe and claim as my invention.